Interactive Effects of Paraoxon and Pyridostigmine on Blood-Brain Barrier Integrity and Cholinergic Toxicity
The effect of the organophosphorous insecticide paraoxon on the integrity of the blood-brain barrier (BBB) and permeability of pyridostigmine (PYR), a peripheral inhibitor of cholinesterase activity, was examined in Long Evans rats. The integrity of the BBB was examined by measuring the number of ca...
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Published in | Toxicological sciences Vol. 78; no. 2; pp. 241 - 247 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Oxford University Press
01.04.2004
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Subjects | |
Online Access | Get full text |
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Summary: | The effect of the organophosphorous insecticide paraoxon on the integrity of the blood-brain barrier (BBB) and permeability of pyridostigmine (PYR), a peripheral inhibitor of cholinesterase activity, was examined in Long Evans rats. The integrity of the BBB was examined by measuring the number of capillaries leaking horseradish peroxidase, which was injected into the heart. Treatment with paraoxon at 100 μg/kg, intramuscularly, resulted in a 3- to 4-fold increase in the number of leaky capillaries in young rats (25 to 30 days old) but not in older rats (90 days old). Interestingly, young rats treated with PYR (30 mg/kg, po) 50 min before treatment with paraoxon showed an inhibited effect of paraoxon on the BBB. Furthermore, no increase in the degree of inhibition of acetylcholinesterase activity was observed in young rats treated with PYR before paraoxon compared with young rats treated with paraoxon alone. Cholinergic toxicity, as assessed by changes in behavior, was not observed in young rats treated with paraoxon alone; but, slight signs of cholinergic toxicity were observed in rats treated with PYR. Young rats treated with both PYR and paraoxon did not exhibit more extensive signs of toxicity than rats treated with paraoxon alone or PYR alone. The results indicate that treatment with paraoxon can compromise BBB permeability at dosages that do not induce cholinergic toxicity, but only in young rats. Also, PYR pre-exposure appears to protect the BBB from the paraoxon-induced alterations. |
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Bibliography: | 1To whom correspondence should be addressed at Kennedy Krieger Institute, Johns Hopkins University, Baltimore, MD 21205. Fax: (443) 923-2695. E-mail: bressler@kennedykrieger.org istex:CB2B65F0AC298853ED580FA040C7939717306489 ark:/67375/HXZ-F1P1G8HJ-5 local:KFH076 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 1096-6080 1096-0929 1096-0929 |
DOI: | 10.1093/toxsci/kfh076 |